Generally, when a drug is administered to a living body, it reaches an affected site and exerts its pharmacological effects at that affected site, thereby exerting its therapeutic effects. On the other hand, even if the drug reaches tissue other than the affected site (that is, normal tissue), it will not be therapeutic.
Therefore, how to guide the drug to the affected site is important. A technique to guide the drug to the affected site is called drug delivery, which has been actively studied and developed recently. This drug delivery has at least two advantages.
One advantage is that a sufficiently high drug concentration can be obtained at the affected site tissue. Pharmacological effects will not be seen unless the drug concentration at the affected site is a constant value or more. The therapeutic effects cannot be expected if the concentration is low.
The second advantage is that the drug is guided to only the affected site tissue and, therefore, adverse reactions to the normal tissue can be inhibited.
Such drug delivery is most effective for a cancer treatment by antitumor agents. Most antitumor agents inhibit the cell growth of cancer cells which divide actively, so that the antitumor agents will also inhibit the cell growth of even the normal tissue in which cells divide actively, such as bone marrow, hair roots, or alimentary canal mucosa.
Therefore, cancer patients to whom the antitumor agents are administered suffer adverse reactions such as anemia, hair loss, and vomiting. Since such adverse reactions impose heavy burdens on the patients, the dosage needs to be limited, thereby causing a problem of incapability to sufficiently obtain the pharmacological effects of the antitumor agents.
Alkylating anti-cancer drugs among such antineoplastic drugs are a generic term for antitumor agents having the ability to combine an alkyl group (—CH2—CH2—) with, for example, a nucleic acid protein. It alkylates DNA and inhibits DNA replication, causing cell death.
This action works regardless of cell cycles, also works on cells of the G0 period, has a strong effect on cells which grow actively, and tends to damage, for example, bone marrow, alimentary canal mucosa, germ cells, or hair roots.
Moreover, antimetabolite antineoplastic drugs are compounds having structures similar to those of nucleic acids or metabolites in a protein synthesis process, impairs cells by, for example, inhibiting synthesis of the nucleic acids, and specifically acts on cells of a mitotic period.
Furthermore, antitumor antibiotics are chemical substances produced by microorganisms, have actions such as DNA synthesis inhibition and DNA strand breaking, and exhibit antitumor activity.
Also, microtubule inhibitors have antitumor effects by directly acting on microtubules that serve important roles to maintain normal functions of cells, for example, by forming spindles during cell division, locating cell organelles, and transporting substances. The microtubule inhibitors act on cells, which divide actively, and nerve cells.
Moreover, platinum drug inhibit DNA synthesis by forming DNA strands, interchain bonds, or DNA protein bonds. Cisplatin is a representative drug, but it causes severe renal injury and requires a large amount of fluid replacement.
Furthermore, hormone preparation antineoplastic drugs are effective against hormone-dependent tumors. Female hormones or anti-androgen drugs are administered to an androgen-dependent prostatic cancer.
Also, molecular targeted drugs is a treatment targeted at molecules that correspond to molecular biological characters specific to respective malignant tumors.
Moreover, topoisomerase inhibitors are enzymes for temporarily generating breaks in DNA and changing the number of tangles of DNA strands. A topoisomerase inhibitor I is an enzyme that generates breaks in one strand of a circular DNA, lets the other strand pass, and then closes the breaks; and a topoisomerase inhibitor II temporarily breaks both the two strands of the circular DNA, lets other two DNA strands pass between the former two strands, and reconnects the broken strands.
Furthermore, nonspecific immunopotentiators inhibit an increase of cancer cells by activating the immune system.
Most antitumor agents inhibit the cell growth of cancer cells which divide actively, so that the antitumor agents will also inhibit the cell growth of even the normal tissue in which cells divide actively, such as bone marrow, hair roots, or alimentary canal mucosa. Therefore, cancer patients to whom the antitumor agents are administered suffer adverse reactions such as anemia, hair loss, and vomiting.
Since such adverse reactions impose heavy burdens on the patients, the dosage needs to be limited, thereby causing a problem of incapability to sufficiently obtain the pharmacological effects of the antitumor agents. Furthermore, in a worst-case scenario, there is a possibility that the patients might die due to the adverse reactions.
So, it is expected to inhibit the adverse reactions and perform the cancer treatment effectively by guiding the antitumor agents to the cancer cells by means of the drug delivery and allowing the antitumor agents exert the pharmacological effects intensively on the cancer cells. Topical anesthetics have the same type of problem.
Topical anesthetics are used to treat topical itches and pains of, for example, mucosa or skin caused by hemorrhoidal disease, stomatitis, gum disease, cavities, tooth extraction, or operations. Lidocaine (product name: xylocalne) is known as a representative topical anesthetic; however, lidocaine is faster-acting, but has an antiarrhythmic effect.
Furthermore, if lidocaine which is an anesthetic is injected into the spinal fluid when giving spinal anesthesia, lidocaine will spread through the spinal fluid; and in a worst-case scenario, there is fear that lidocaine might reach a cervical part of the spinal cord and thereby cause a respiratory function to stop and bring about critical adverse effects.
So, it is expected to inhibit the adverse reactions and perform the cancer treatment effectively by guiding the antitumor agents to the cancer cells by means of the drug delivery and allowing the antitumor agents exert the pharmacological effects intensively on the cancer cells.
Furthermore, it is also expected to prevent the spread of the topical anesthetic and achieve continued medicinal effects and reduction of the adverse effects by means of the drug delivery.
An example of a specific method for the drug delivery is the use of a carrier. This is to load the carrier, which tends to concentrate on the affected site, with the drug and have the carrier carry the drug to the affected site.
A promising candidate of the carrier is a magnetic substance and there is a suggested method of attaching the carrier, which is the magnetic substance, to the drug and allowing the carrier to be accumulated at the affected site by a magnetic field (see, for example, Patent Literature 1).
However, when using the magnetic substance carrier as the carrier, it has been found that it is difficult to aurally administer the magnetic substance carrier, molecules of the carrier are generally giant, and there are technical problems about binding strength and affinity between the carrier and the drug molecules; and it is originally difficult to achieve the practical use of the magnetic substance carrier.
Therefore, the inventors of the present invention suggested a topical anesthetic in which side chains for giving positive or negative spin charge density are bonded to a basic skeleton of an organic compound, and which has suitability as a whole insofar as the topical anesthetic is guided, by means of magnetic sharing, by an external magnetic field; and if the topical anesthetic is applied to a human body or an animal, it is retained in an area where a magnetic field is applied topically by the magnetic field outside the body and the medicinal effects that the topical anesthetic originally has are exerted on the area. The above-mentioned publication describes the iron-salen complex as an example of such a drug (see Patent Literature 2).
An antitumor drug containing an iron-salen complex is also disclosed (see, for example, Patent Literature 3).